PPARgamma-targeting Nanomedicine for the Treatment of Atherosclerotic Plaque Rupture

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19384
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyushu University
• Principal Investigator: Junchiro Koga 九州大学, 循環器病未来医療研究センター, 学術研究員 (10746142)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 分子血管学 / 動脈硬化 / ナノメディスン

Outline of Final Research Achievements

Objective―Inflammatory monocytes/macrophages produce various proteinases and induce rupture of atherosclerotic plaques. We have tested a hypothesis that nanoparticle-mediated delivery of peroxisome proliferator-activated receptor-γ agonist pioglitazone to monocytes/macrophages inhibits plaque ruptures.
Approach and Results―Poly(lactic-co-glycolic-acid) nanoparticles (NPs) were prepared for targeting delivery to monocytes/macrophages. Weekly intravenous administration of pioglitazone-NPs decreased buried fibrous caps, suggesting healed ruptures, in the brachiocephalic arteries of Apoe－/－ mice with a high-fat diet and angiotensin II infusion. Pioglitazone-NPs also inhibited the activity of proteases and decreased expression of inflammatory cytokines in macrophages.
Conclusions―Nanoparticle-mediated delivery of pioglitazone inhibited macrophage activation and plaque ruptures in ApoE-/- mice. These results demonstrate a promising strategy to prevent atherosclerotic plaque ruptures.

Free Research Field

循環器内科学